In vivo studies on cytokine involvement during acute viral respiratory disease of swine: troublesome but rewarding

Abstract

The early cytokines interferon-alpha (IFN-alpha), tumour necrosis factor-alpha (TNF-alpha), interleukin-1, -6 and -8 (IL-1, -6, -8) are produced during the most early stage of an infection. The activities of these cytokines have been studied extensively in vitro and in rodents, but in vivo studies on the role of these cytokines in infectious diseases of food animals are few. This review concentrates on in vivo studies of cytokine involvement in infectious respiratory diseases of swine, with an emphasis on viral infections. First evidence for the role of early cytokines in pneumonia in swine came from experimental infections with Mycoplasma hyopneumoniae and Actinobacillus pleuropneumoniae. The role of TNF-alpha and IL-1 in the symptoms and pathology of porcine pleuropneumonia has recently been proven by use of an adenovirus vector expressing the anti-inflammatory IL-10. In the authors' laboratory, studies were undertaken to investigate the relationship between viral respiratory disease and bioactive lung lavage levels of IFN-alpha, TNF-alpha, IL-1 and IL-6. Out of three respiratory viruses-porcine respiratory coronavirus (PRCV), porcine reproductive and respiratory syndrome virus (PRRSV) and swine influenza virus (SIV)-only SIV induced acute respiratory disease and severe lung damage by itself. Disease and lung pathology were tightly associated with the simultaneous production of IFN-alpha, TNF-alpha, IL-1 and IL-6. In challenge studies of SIV-vaccinated pigs, levels of IFN-alpha, TNF-alpha and IL-6, but not IL-1 were correlated with clinical and virological protection. Multifactorial respiratory disease was reproduced by combined inoculations with PRCV or PRRSV followed by LPS from Escherichia coli. In comparison with the respective single inoculations, which were subclinical, there was a true potentiation of disease and production of TNF-alpha, IL-1 and IL-6. TNF-alpha and IL-6 were best correlated with disease. In further studies, we will use more specific strategies to dissect the role of cytokines during viral infections.

Increased Production of Proinflammatory Cytokines following Infection with Porcine Reproductive and Respiratory Syndrome Virus andMycoplasma hyopneumoniae

“…The results of the study presented here confirm that M. hyopneumoniae appears to induce greater levels of the proinflammatory cytokines than PRRSV. In contrast, an earlier in vivo study showed that PRRSV did not induce proinflammatory cytokine production as effectively as swine influenza virus (34). PRRSV infection has been reported to induce minimal TNF-␣ at 10 dpi (33), which was confirmed in this study.…”

“…Proinflammatory cytokines are believed to play an important role in porcine respiratory disease by coordinating and activating the adaptive immune response, which enables the host to eliminate offending pathogens (14,21,33,34). However, if cytokine levels become excessive, tissue damage and even death of the host can occur.…”

Lung Cell Tropism and Inflammatory Cytokine-Profile of Porcine Respiratory Coronavirus Infection

“…We have previously shown that PRCV induces a different cytokine profile when compared to primary respiratory viral pathogens like swine influenza virus [14][15][16]. The latter virus induces much more rapid and higher production of a series of proinflammatory cytokinesinterferon-(IFN-), interleukin-1 (IL-1), IL-6 and tumour necrosis factor-(TNF-) -after intratracheal inoculation and this may explain the much more prominent respiratory disease as compared to PRCV [14,15]. In previous studies, however, cytokines were only examined during the first 3-4 days after inoculation with PRCV.…”

Elastase-Dependent Live Attenuated Swine Influenza A Viruses Are Immunogenic and Confer Protection against Swine Influenza A Virus Infection in Pigs

“…The cytokines tumor necrosis factor alpha (TNF-␣), IFN-␣, IL-1␤, and IL-6 are produced in the lungs during SIV infection and are involved in lung pathology (45,49). Supernatants from lungs after tissue homogenization were subjected to ELISA to determine the cytokine levels in the lungs.…”

“…There is growing evidence that the early cytokines are the cause of the clinical signs and the lung epithelial damage as- sociated with swine influenza (47)(48)(49). Early cytokines are produced by nonimmune cells at the site of infection, and these cytokines are responsible for local inflammatory reactions, as well as some systemic effects.…”